Mesoreodon megalodon was named by Peterson (1907). Its type specimen is CM 1325, a partial skull (front of the skull and lower jaws of a young individual, but with all the permanent teeth in position), and it is a 3D body fossil. Its type locality is Lower Monroe Creek, which is in an Arikareean terrestrial horizon in Nebraska.

If no rank is listed, the taxon is considered an unranked clade in modern classifications. Ranks may be repeated or presented in the wrong order because authors working on different parts of the classification may disagree about how to rank taxa.

Small size; infra-orbital foramen above posterior part of P3; bullæ compressed, not extending below postglenoid process; steop basicranial axis; p 2 and P 3 crowded, unreduced; inferior border of ramus turns sharply downward below anterior part of M3 ; zygomatic arch narrow immediately in advance of the glenoid process, continuing forward and upward in a strong convexity on the side of face, more as in Eporeodon than in Promerycochoerus lacrymal fossæ deep but small; depth of malar below orbit, 29 mm.; hypocone of M3 noticeably smaller than protocone; internal cingulum on superior molars but faintly developed; transverse crests near together; very strong convexity above foramen magnum; crest of zygoma low and directly above glenoid process. Shape of the canine more like that of a carnivore than an herbivore.

SKULL: Larger, more massive, and broader than examples of M. cheeki; approximately equal in length to that of M. chelonyx wheeleri but broader; sagittal crest higher than in M. cheeki; frontals wide; malar deep below the orbit; zygomatic arch more massive and extending upward and posteriorly farther than in examples of M. cheeki,·lacrimal fossa larger than in examples of M. cheeki; infra- orbital foramen located above the posterior portion of pa and extending to the anterior portion of P 4 ; paroccipital process wide at base, and wider and tapering more rapidly than in examples of M. cheeki; bulla well nflated, comparatively large and suboval in outline, larger than in examples of M. cheeki; postglenoid process more robust and wider transversely than in examples of M. cheeki.
MANDIBLE: More massive than examples of M. cheeki.
DENTITION: Dental series longer and heavier than in examples of M. cheeki.
LIMBS: Longer and heavier than in M. cheeki